Oral pyrroloquinoline quinone (PQQ) during pregnancy increases cardiomyocyte endowment in spontaneous IUGR guinea pigs.
Oral pyrroloquinoline quinone (PQQ) during pregnancy increases cardiomyocyte endowment in spontaneous IUGR guinea pigs.
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DOI：
10.1017/s2040174423000053
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发表时间：
2023-06
影响因子：
1.7
通讯作者：
Stansfield, Brian K.
中科院分区：
文献类型：
--
作者：
Mattern, Jordan;Gemmell, Andrew;Allen, Paige E.;Mathers, Katherine E.;Regnault, Timothy R. H.;Stansfield, Brian K.
宫内生长受限（IUGR）对发育中的心肌细胞产生负面影响，新的证据表明氧化应激途径的激活在这种改变的发育中发挥着关键作用。在这里，我们为怀孕的豚鼠母猪在妊娠后半期提供了 PQQ（一种芳香族三环邻醌，具有氧化还原辅助因子抗氧化剂的作用），作为 IUGR 相关心肌病的潜在抗氧化剂干预措施。怀孕的豚鼠母猪在妊娠中期被随机分配接受 PQQ 或安慰剂，胎儿被确定为自发 IUGR (spIUGR) 或近期正常生长 (NG)，产生四个队列：NG ± PQQ 和 spIUGR ± PQQ。制备胎儿左心室和右心室的横截面并分析心肌细胞数量、胶原沉积、增殖（Ki-67）和凋亡（TUNEL）。与 NG 相比，spIUGR 胎儿心脏的心肌细胞禀赋降低；然而，PQQ 对 spIUGR 心脏中的心肌细胞数量产生积极影响。与 NG 动物相比，spIUGR 心室中经历增殖和凋亡的心肌细胞更常见，补充 PQQ 后心肌细胞显着减少。同样，spIUGR 脑室中的胶原沉积增加，而在 PQQ 处理的 spIUGR 动物中，胶原沉积得到部分挽救。妊娠母猪产前施用 PQQ 可以抑制 spIUGR 对分娩过程中心肌细胞数量、细胞凋亡和胶原沉积的负面影响。这些数据确定了一种针对不可逆 spIUGR 相关心肌病的新型治疗干预措施。
Intrauterine growth restriction (IUGR) exerts a negative impact on developing cardiomyocytes and emerging evidence suggests activation of oxidative stress pathways plays a key role in this altered development. Here, we provided pregnant guinea pig sows with PQQ, an aromatic tricyclic o-quinone that functions as a redox cofactor antioxidant, during the last half of gestation as a potential antioxidant intervention for IUGR-associated cardiomyopathy. Pregnant guinea pig sows were randomly assigned to receive PQQ or placebo at mid gestation and fetuses were identified as spontaneous IUGR (spIUGR) or normal growth (NG) near term yielding four cohorts: NG ± PQQ and spIUGR ± PQQ. Cross sections of fetal left and right ventricles were prepared and cardiomyocyte number, collagen deposition, proliferation (Ki-67) and apoptosis (TUNEL) were analyzed. Cardiomyocyte endowment was reduced in spIUGR fetal hearts when compared to NG; however, PQQ exerted a positive effect on cardiomyocyte number in spIUGR hearts. Cardiomyocytes undergoing proliferation and apoptosis were more common in spIUGR ventricles when compared with NG animals, which was significantly reduced with PQQ supplementation. Similarly, collagen deposition was increased in spIUGR ventricles and was partially rescued in PQQ-treated spIUGR animals. The negative influence of spIUGR on cardiomyocyte number, apoptosis, and collagen deposition during parturition can be suppressed by antenatal administration of PQQ to pregnant sows. These data identify a novel therapeutic intervention for irreversible spIUGR-associated cardiomyopathy.